cannabidiol and Developmental-Disabilities

There is a great deal of interest in the potential symptomatic benefits of medicinal cannabis among parents of children and adolescents with developmental disorders.. This article provides an overview of what is known about medicinal cannabis as a treatment for paediatric developmental disorders.. While there is emerging evidence in support of medicinal cannabis for some adult mental health disorders, to date the evidence in children and adolescents is scant. Reports from uncontrolled observational studies suggest that cannabidiol-rich products may be helpful in reducing behavioural problems in autistic youth. Cannabidiol appears to have a relatively benign adverse effect profile and therefore may be worth considering as a treatment option in some cases. Several controlled clinical trials are underway that will provide more definitive information on the therapeutic value of medicinal cannabis in paediatric developmental and behavioural disorders.

Topics: Adolescent; Adult; Cannabidiol; Cannabinoids; Cannabis; Child; Child Behavior Disorders; Developmental Disabilities; Humans; Problem Behavior

Developmental and epileptic encephalopathies (DEEs) are the most severe group of drug-resistant epilepsies. Alternatives to oral therapies are urgently needed to reduce seizures and improve developmental outcomes and comorbidities in this medically complex population.. To assess the safety and tolerability of cannabidiol (CBD) transdermal gel in children with DEEs and to evaluate seizure frequency, sleep, and quality of life.. This nonrandomized controlled trial was conducted in 2 centers in Australia and New Zealand from April 2018 to July 2019. Children and adolescents aged 3 to 18 years with DEEs who were receiving a stable regimen of 1 to 4 antiseizure medications were eligible for this study. After 1-month baseline and titration periods, patients entered a 5.5-month flexible-dosing maintenance period for a total of 6.5 months of treatment. Data were analyzed throughout the 6.5-month treatment period.. Twice-daily applications of CBD transdermal gel at doses of 125 to 500 mg for 6.5 months.. Safety and tolerability assessments included adverse events (AEs) and examination of skin. The outcome for seizures was the median percentage change from baseline in monthly (28-day) seizure frequency of focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) over 6.5 months.. Of 48 patients (mean [SD] age, 10.5 [3.8] years; 26 [54%] boys), 29 (60%) had at least 1 treatment-related AE over 6.5 months; 44 of 46 treatment-related AEs (96%) were mild or moderate. Treatment-related AEs that occurred in at least 5% of patients were application-site dryness, application-site pain, and somnolence (each reported by 4 patients [8%]). The only treatment-related gastrointestinal AE was diarrhea, reported in a single patient. CBD treatment was associated with reductions in FIAS and TCS frequency. Analysis of the 33 patients with FIAS and TCS showed a median (interquartile range) monthly reduction in seizures of 58% (-5.3% to 81.8%) at 5 months and 43.5% (-23.8% to 57.5%) over the entire 6.5-month study period. Parents and caregivers noted improvements in social or interpersonal engagement and irritability (33 of 43 [77%] participants); alertness, energy, and sleep (23 of 43 [53%]); and cognition or concentration (20 of 43 [47%]).. In this study, CBD transdermal gel was safe, well tolerated, and was associated with reductions in FIAS and TCS frequency and disease burden.. ClinicalTrials.gov Identifier: ACTRN12618000516280.

Topics: Administration, Cutaneous; Adolescent; Anticonvulsants; Australia; Cannabidiol; Child; Child, Preschool; Developmental Disabilities; Drug Resistant Epilepsy; Female; Gels; Humans; Male; New Zealand; Seizures; Treatment Outcome

Pathogenic variants in AIMP1 gene are rare causes of neurologic disorders. Homozygous frameshift and nonsense variants in AIMP1 have been described in severe neurodegenerative disease. This is the third report of a homozygous nonsense variant in AIMP1 [c.115 C > T (p.Gln39*)] in a girl with severe neonatal onset epileptic encephalopathy. Like the two other cases reported, our patient is also of Filipino descent. Clinical features include microcephaly, poor visual motor development, shallow breathing, severe hypertonia in extremities, severe global developmental delay, poor gag and suck reflex, failure to thrive in the neonatal period, and early onset intractable seizures. Brain MRI showed hypoplasia of corpus callosum as well as cerebellar vermis, global volume loss and diminished myelination for her age. Electroencephalogram at four months of age showed background consisting of synchronous and asynchronous intervals of burst suppression with intermittent multifocal spikes predominantly in the bi-temporal region, suggestive of Early Onset Epileptic Encephalopathy with Burst Suppression (EOEE-BS) which has not been previously associated with the c.115 C > T variant in AIMP1. Of note, she presented to us in super refractory status epilepticus which was eventually controlled after administration of ketogenic diet and Epidiolex (cannabidiol). This report expands the genetic landscape of EOEE-BS. This is the first case of this specific variant in which Epidiolex was administered, which along with Ketogenic diet aided in controlling patient's super refractory status epilepticus.

Topics: Anticonvulsants; Brain; Brain Waves; Cannabidiol; Codon, Nonsense; Cytokines; Developmental Disabilities; Diet, Ketogenic; Epilepsy; Female; Homozygote; Humans; Infant; Neoplasm Proteins; RNA-Binding Proteins